B6.C congenic strains of mice, possessing chromosomal segments from high-responding BALB/cByJ (C) mice on the genetic background of low-responding C57BL/6ByJ (B6) mice, were examined for their ability to make an antibody response to Type III pneumococcal polysaccharide (SSS-III) and the alpha 1 yield 3 determinant of bacterial (Leuconostoc) dextran B-1355. The results obtained affirmed that genes making a positive contribution to responsiveness to SSS-III are located on different chromosomes, i.e., chromosomes 1,3,4,5, and 9. At least one other gene also influences responsiveness to this antigen; it it closely linked to the H-17 locus which has not yet been assigned to a specific chromosome. Genes on chromosomes 1,4, and 5 were found to influence the magnitude of the antibody response to dextran B-1355. Some of these genes appear to be antigen-specific in their mode of action; however, others are not since they exert an influence on the antibody response to both SSS-III and dextran B-1355.